Primary taste sensations (sweet, sour, bitter, salt, and umami) are often associated with different types of foods. For example, umami taste often signals food rich in proteins and certain L-amino acids. However, the basis of these sensations is controversial and not well understood. Molecular and limited behavioral studies have identified a candidate taste receptor, T1R1/T1R3, which detects umami stimuli, including monosodium glutamate, and many more L-amino acids. In contrast, other molecular and behavioral studies report evidence that L-AP4 (a potent mGluR4 agonist) elicits afferent signals that mimic umami stimulation, suggesting that a taste-mGluR4 receptor is involved in umami taste. This controversy is fueled by studies with mice lacking T1R3. One study reported that T1R3 knockout mice completely eliminated umami taste (Zhao et al., 2003), whereas another study with independently developed T1R3 knockout mice reported only a reduction in umami taste (Damak et al., 2003). Pilot threshold experiments with T1R3 knockout mice obtained from Damak et al. found that these mice can taste monosodium glutamate nearly as well as wild type mice of the same genetic background. In addition, preliminary studies with rats show that mGluR4 antagonists alter the taste of L-glutamate but have little effect on the taste of the amino acid L-arginine. These data, along with other studies, suggest that receptors other than T1R3 contribute to umami taste. Two Specific Aims in this proposal will test the hypothesis that some L-amino acids (e.g., L-glutamate) are detected by two receptors (T1R1/T1R3, taste-mGluR4) and other L-amino acids (e.g., L-arginine) are detected by one receptor (T1R1/T1R3). Specific Aim 1 will determine how similar the taste qualities of three L-amino acids (L-glutamate, L-arginine, and L-alanine) are in wild type and T1R3 knockout mice by assessing: a) taste thresholds for these substance, b) perceptual similarities between these substances using conditioned taste aversion methods, and c) perceptual differences between these substances using discrimination methods. Specific Aim 2 will examine the effects of mGluR4 antagonists on the taste qualities of these amino acids in wild type and T1R3 knockout mice using the same behavioral methods. The behavioral profiles developed from these experiments with knockout and wild-type mice will provide new insights into the roles of T1R3 and taste-mGluR4 receptors in afferent signaling of these amino acids. An understanding of these taste transduction mechanisms can have tremendous health care implications when applied to regulation of food intake by nutritionally challenged individuals (e.g., diabetics, cardiovascular disease, aged).